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Progression of brain cholinergic dysfunction in patients with isolated rapid eye movement sleep behavior disorder

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Title: Progression of brain cholinergic dysfunction in patients with isolated rapid eye movement sleep behavior disorder
Authors: Staer, Kristian, Iranzo, Alex, Terkelsen, Miriam Højholt, Stokholm, Morten Gersel, Danielsen, Erik Hvid, Østergaard, Karen, Serradell, Mónica, Otto, Marit, Svendsen, Kristina B, Garrido, Alicia, Vilas, Dolores, Santamaria, Joan, Møller, Arne, Gaig, Carles, Brooks, David J, Borghammer, Per, Tolosa, Eduardo, Pavese, Nicola
Source: Staer, K, Iranzo, A, Terkelsen, M H, Stokholm, M G, Danielsen, E H, Østergaard, K, Serradell, M, Otto, M, Svendsen, K B, Garrido, A, Vilas, D, Santamaria, J, Møller, A, Gaig, C, Brooks, D J, Borghammer, P, Tolosa, E & Pavese, N 2024, 'Progression of brain cholinergic dysfunction in patients with isolated rapid eye movement sleep behavior disorder', European Journal of Neurology, vol. 31, no. 1, e16101. https://doi.org/10.1111/ene.16101
Publication Year: 2024
Collection: Aarhus University: Research
Subject Terms: Parkinson's disease, REM sleep behavior disorder, biomarkers, cognition, positron emission tomography, Parkinson Disease, Brain/diagnostic imaging, Donepezil, Humans, Acetylcholinesterase, REM Sleep Behavior Disorder/psychology
Description: BACKGROUND: Reduced cortical acetylcholinesterase activity, as measured by 11 C-donepezil positron emission tomography (PET), has been reported in patients with isolated rapid eye movement (REM) sleep behavior disorder (iRBD). However, its progression and clinical implications have not been fully investigated. Here, we explored the relationship between longitudinal changes in brain acetylcholinesterase activity and cognitive function in iRBD. METHODS: Twelve iRBD patients underwent 11 C-donepezil PET at baseline and after 3 years. PET images were interrogated with statistical parametric mapping (SPM) and a regions of interest (ROI) approach. Clinical progression was assessed with the Movement Disorder Society-Unified Parkinson's Disease Rating Scale-Part III (MDS-UPDRS-III). Cognitive function was rated using the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA). RESULTS: From baseline to follow-up, the mean 11 C-donepezil distribution volume ratio (DVR) decreased in the cortex (p = 0.006), thalamus (p = 0.013), and caudate (p = 0.013) ROI. Despite no significant changes in the group mean MMSE or MoCA scores being observed, individually, seven patients showed a decline in their scores on these cognitive tests. Subgroup analysis showed that only the subgroup of patients with a decline in cognitive scores had a significant reduction in mean cortical 11 C-donepezil DVR. CONCLUSIONS: Our results show that severity of brain cholinergic dysfunction in iRBD patients increases significantly over 3 years, and those changes are more severe in those with a decline in cognitive test scores.
Document Type: article in journal/newspaper
File Description: application/pdf
Language: English
ISSN: 1351-5101
1468-1331
Relation: info:eu-repo/semantics/altIdentifier/pmid/37847229; info:eu-repo/semantics/altIdentifier/pissn/1351-5101; info:eu-repo/semantics/altIdentifier/eissn/1468-1331
DOI: 10.1111/ene.16101
Availability: https://pure.au.dk/portal/en/publications/f7e7d9da-f0a7-4d2a-bc46-6b5da390fe61
https://doi.org/10.1111/ene.16101
https://pure.au.dk/ws/files/444992272/Euro_J_of_Neurology_-_2023_-_St_r_-_Progression_of_brain_cholinergic_dysfunction_in_patients_with_isolated_rapid_eye.pdf
Rights: info:eu-repo/semantics/openAccess ; http://creativecommons.org/licenses/by-nc-nd/4.0/
Accession Number: edsbas.2D74AC40
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  Data: Progression of brain cholinergic dysfunction in patients with isolated rapid eye movement sleep behavior disorder
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  Data: <searchLink fieldCode="AR" term="%22Staer%2C+Kristian%22">Staer, Kristian</searchLink><br /><searchLink fieldCode="AR" term="%22Iranzo%2C+Alex%22">Iranzo, Alex</searchLink><br /><searchLink fieldCode="AR" term="%22Terkelsen%2C+Miriam+Højholt%22">Terkelsen, Miriam Højholt</searchLink><br /><searchLink fieldCode="AR" term="%22Stokholm%2C+Morten+Gersel%22">Stokholm, Morten Gersel</searchLink><br /><searchLink fieldCode="AR" term="%22Danielsen%2C+Erik+Hvid%22">Danielsen, Erik Hvid</searchLink><br /><searchLink fieldCode="AR" term="%22Østergaard%2C+Karen%22">Østergaard, Karen</searchLink><br /><searchLink fieldCode="AR" term="%22Serradell%2C+Mónica%22">Serradell, Mónica</searchLink><br /><searchLink fieldCode="AR" term="%22Otto%2C+Marit%22">Otto, Marit</searchLink><br /><searchLink fieldCode="AR" term="%22Svendsen%2C+Kristina+B%22">Svendsen, Kristina B</searchLink><br /><searchLink fieldCode="AR" term="%22Garrido%2C+Alicia%22">Garrido, Alicia</searchLink><br /><searchLink fieldCode="AR" term="%22Vilas%2C+Dolores%22">Vilas, Dolores</searchLink><br /><searchLink fieldCode="AR" term="%22Santamaria%2C+Joan%22">Santamaria, Joan</searchLink><br /><searchLink fieldCode="AR" term="%22Møller%2C+Arne%22">Møller, Arne</searchLink><br /><searchLink fieldCode="AR" term="%22Gaig%2C+Carles%22">Gaig, Carles</searchLink><br /><searchLink fieldCode="AR" term="%22Brooks%2C+David+J%22">Brooks, David J</searchLink><br /><searchLink fieldCode="AR" term="%22Borghammer%2C+Per%22">Borghammer, Per</searchLink><br /><searchLink fieldCode="AR" term="%22Tolosa%2C+Eduardo%22">Tolosa, Eduardo</searchLink><br /><searchLink fieldCode="AR" term="%22Pavese%2C+Nicola%22">Pavese, Nicola</searchLink>
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  Data: Staer, K, Iranzo, A, Terkelsen, M H, Stokholm, M G, Danielsen, E H, Østergaard, K, Serradell, M, Otto, M, Svendsen, K B, Garrido, A, Vilas, D, Santamaria, J, Møller, A, Gaig, C, Brooks, D J, Borghammer, P, Tolosa, E & Pavese, N 2024, 'Progression of brain cholinergic dysfunction in patients with isolated rapid eye movement sleep behavior disorder', European Journal of Neurology, vol. 31, no. 1, e16101. https://doi.org/10.1111/ene.16101
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  Data: 2024
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  Data: Aarhus University: Research
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  Label: Subject Terms
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  Data: <searchLink fieldCode="DE" term="%22Parkinson's+disease%22">Parkinson's disease</searchLink><br /><searchLink fieldCode="DE" term="%22REM+sleep+behavior+disorder%22">REM sleep behavior disorder</searchLink><br /><searchLink fieldCode="DE" term="%22biomarkers%22">biomarkers</searchLink><br /><searchLink fieldCode="DE" term="%22cognition%22">cognition</searchLink><br /><searchLink fieldCode="DE" term="%22positron+emission+tomography%22">positron emission tomography</searchLink><br /><searchLink fieldCode="DE" term="%22Parkinson+Disease%22">Parkinson Disease</searchLink><br /><searchLink fieldCode="DE" term="%22Brain%2Fdiagnostic+imaging%22">Brain/diagnostic imaging</searchLink><br /><searchLink fieldCode="DE" term="%22Donepezil%22">Donepezil</searchLink><br /><searchLink fieldCode="DE" term="%22Humans%22">Humans</searchLink><br /><searchLink fieldCode="DE" term="%22Acetylcholinesterase%22">Acetylcholinesterase</searchLink><br /><searchLink fieldCode="DE" term="%22REM+Sleep+Behavior+Disorder%2Fpsychology%22">REM Sleep Behavior Disorder/psychology</searchLink>
– Name: Abstract
  Label: Description
  Group: Ab
  Data: BACKGROUND: Reduced cortical acetylcholinesterase activity, as measured by 11 C-donepezil positron emission tomography (PET), has been reported in patients with isolated rapid eye movement (REM) sleep behavior disorder (iRBD). However, its progression and clinical implications have not been fully investigated. Here, we explored the relationship between longitudinal changes in brain acetylcholinesterase activity and cognitive function in iRBD. METHODS: Twelve iRBD patients underwent 11 C-donepezil PET at baseline and after 3 years. PET images were interrogated with statistical parametric mapping (SPM) and a regions of interest (ROI) approach. Clinical progression was assessed with the Movement Disorder Society-Unified Parkinson's Disease Rating Scale-Part III (MDS-UPDRS-III). Cognitive function was rated using the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA). RESULTS: From baseline to follow-up, the mean 11 C-donepezil distribution volume ratio (DVR) decreased in the cortex (p = 0.006), thalamus (p = 0.013), and caudate (p = 0.013) ROI. Despite no significant changes in the group mean MMSE or MoCA scores being observed, individually, seven patients showed a decline in their scores on these cognitive tests. Subgroup analysis showed that only the subgroup of patients with a decline in cognitive scores had a significant reduction in mean cortical 11 C-donepezil DVR. CONCLUSIONS: Our results show that severity of brain cholinergic dysfunction in iRBD patients increases significantly over 3 years, and those changes are more severe in those with a decline in cognitive test scores.
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  Data: 10.1111/ene.16101
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